IFN-γ Production to Leishmania Antigen Supplements the Leishmania Skin Test in Identifying Exposure to L. braziliensis Infection

Background: Cutaneous leishmaniasis due to L. braziliensis (CL) is characterized by a positive delayed type hypersensitivity test (DTH) leishmania skin test (LST) and high IFN-gamma production to soluble leishmania antigen (SLA). The LST is used for diagnosis of CL and for identification of individuals exposed to leishmania infection but without disease. The main aim of the present study was to identify markers of exposure to L. braziliensis infection. Methodolgy/Principal Findings: This cohort study enrolled 308 household contacts (HC) of 76 CL index cases. HC had no active or past history of leishmaniasis. For the present cross-sectional study cytokines and chemokines were determined in supernatants of whole blood culture stimulated with SLA. Of the 308 HC, 36 (11.7%) had a positive LST but in these IFN-gamma was only detected in 22 (61.1%). Moreover of the 40 HC with evidence of IFN-gamma production only 22 (55%) had a positive LST. A total of 54 (17.5%) of 308 HC had specific immune response to SLA. Only a moderate agreement (Kappa = 0.52; 95% CI: 0.36-0.66) was found between LST and IFN-gamma production. Moreover while enhancement of CXCL10 in cultures stimulated with SLA was observed in HC with DTH+ and IFN-gamma+ and in patients with IFN-gamma(+) and DTH-, no enhancement of this chemokine was observed in supernatants of cells of HC with DTH+ and IFN-gamma(-). Conclusions/Significance: This study shows that in addition of LST, the evaluation of antigen specific IFN-gamma production should be performed to determine evidence of exposure to leishmania infection. Moreover it suggests that in some HC production of IFN-gamma and CXCL10 are performed by cells not involved with DTH reaction.